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Cryptococcal MeningitisPhase 4ORCASNCT01535469

Operational Research for Cryptococcal Antigen Screening

A Phase 4 study testing Fluconazole in people with Cryptococcal Meningitis and Cryptococcus Neoformans, run by University of Minnesota at 2 sites in Uganda.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This will be a stepped wedge randomized trial design to evaluate the implementation of cryptococcal antigen (CRAG) screening and preemptive anti-fungal therapy of HIV-infected persons entering antiretroviral therapy (ART) outpatient treatment in Uganda. Read more about this study

Who is it for?
Ages 14 years and older
What is being tested?
Fluconazole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3,049 participants
Where
2 sitesUganda
Study dates
1 Jul 2012to Jun 2015
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 14 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • HIV-1 infection
  • CD4≤100 cells/mcL
  • Cryptococcal antigen (CRAG) positive
  • age >14 years

Who cannot join

  • Suspected Cryptococcal meningitis
  • Prior known history of cryptococcal meningitis
  • currently receiving HIV antiretroviral therapy
  • Allergy to any azole antifungal medication
  • Persons with known serious hepatic co-morbidities, transaminitis, or clinical jaundice who should not receive fluconazole in the opinion of the study investigator.
  • Current known pregnancy

Trial locations and contacts

2 sites in 1 country.

Uganda2 sites

  • Infectious Disease Institute, Makerere University

    Kampala

  • Kampala Capital Council Authority Clinics

    Kampala

Other trials in Uganda

About this study

Official title: Operational Research for Cryptococcal Antigen Screening to Improve ART Survival

This will be a stepped wedge randomized trial design to evaluate the implementation of cryptococcal antigen (CRAG) screening and preemptive anti-fungal therapy of HIV-infected persons entering antiretroviral therapy (ART) outpatient treatment in Uganda. Those who are ART eligible with a CD4≤100 cells/mcL will have a serum/plasma CRAG performed by lateral flow assay. Those who are CRAG-positive and asymptomatic will be treated with high dose fluconazole. After 6 months survival with retention-in-care will be compared between those who are CRAG+ and CRAG negative

Being tested
Fluconazole
Keywords
cryptococcal meningitis, hiv, aids, implementation science, stepped wedge design, retention-in-care
Medical subject headings
Meningitis, Cryptococcal, Cryptococcosis, Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FluconazoleDrug

    Also called Diflucan

    Fluconazole 800mg orally daily for 2 weeks, then 400mg daily for 8 weeks

Study groups in NCT01535469
Study groupRoleWhat they receive
CrAg Screening and FluconazoleExperimentalCryptococcal Antigen (CrAg) Screening with preemptive antifungal treatment per World Health Organization (WHO) guidelines. Randomized Stepped Wedge design of phased implementation.
Receives: Drug: Fluconazole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Retention in care

    1. before/after CRAG screening implementation (All persons)
    2. CRAG positive persons treated with high-dose fluconazole as compared to 6-month survival of CRAG negative persons who are eligible for antiretroviral therapy.

    Measured: 6-month

Secondary outcomes (7)

  1. Cryptococcal meningitis-free survival time

    Cryptococcal meningitis-free survival time in those who are asymptomatic CRAG positive and treated with fluconazole compared to CRAG-negative persons with CD4<100 cells/mcL

    Measured: 6-month

  2. Survival Time

    Survival time among CRAG+ vs. CRAG negative persons with CD4<100 cells/mcL.

    Measured: 6-month

  3. Uptake of CRAG screening and preemptive treatment

    Measured: baseline

  4. Time from CRAG+ test to receipt of fluconazole therapy

    Measured: Days from CD4 testing

  5. All-cause discontinuation of fluconazole

    Number of participants with early discontinuation of fluconazole for any reason (e.g. non-compliance, adverse event)

    Measured: 6-month

  6. Percentage of participants with symptomatic cryptococcal meningitis

    Measured: baseline

  7. Risk factors for symptomatic cryptococcal meningitis

    Measured: baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2012 (estimated)
  2. Study start1 Jul 2012
  3. Primary completionJun 2015
  4. Study completionJun 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
3,049 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01535469
Sponsor's protocol ID
HS1254
Other IDs
U01GH000517
Acronym
ORCAS
Status last verified
Jun 2020
First submitted
10 Feb 2012
Last updated
4 Jun 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: After publication, data to be shared upon request to the Infectious Disease Institute Research Department as per the institutional data sharing policy.

Publications

  • Rajasingham R, Meya DB, Boulware DR. Integrating cryptococcal antigen screening and pre-emptive treatment into routine HIV care. J Acquir Immune Defic Syndr. 2012 Apr 15;59(5):e85-91. doi: 10.1097/QAI.0b013e31824c837e.

    PubMed 22410867

  • Meya DB, Manabe YC, Castelnuovo B, Cook BA, Elbireer AM, Kambugu A, Kamya MR, Bohjanen PR, Boulware DR. Cost-effectiveness of serum cryptococcal antigen screening to prevent deaths among HIV-infected persons with a CD4+ cell count < or = 100 cells/microL who start HIV therapy in resource-limited settings. Clin Infect Dis. 2010 Aug 15;51(4):448-55. doi: 10.1086/655143.

    PubMed 20597693

  • Meya DB, Kiragga AN, Nalintya E, Morawski BM, Rajasingham R, Park BJ, Mubiru A, Kaplan JE, Manabe YC, Boulware DR. Reflexive Laboratory-Based Cryptococcal Antigen Screening and Preemptive Fluconazole Therapy for Cryptococcal Antigenemia in HIV-Infected Individuals With CD4 <100 Cells/microL: A Stepped-Wedge, Cluster-Randomized Trial. J Acquir Immune Defic Syndr. 2019 Feb 1;80(2):182-189. doi: 10.1097/QAI.0000000000001894.

    PubMed 30399034

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Fluconazole in people with Cryptococcal Meningitis and Cryptococcus Neoformans, run by University of Minnesota at 2 sites in Uganda.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Retention in care (time frame: 6-month). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01535469, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2020.

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